Interaction of Neuropeptide Y and the Sympathetic Nervous System in Vascular Control in Man John Clarke, MRCPI;

Benjamin, Nigel MRCP
Larkin, Simon BSc
Webb, David MRCP
Maseri, Attilio MD, FACC
Davies, Graham MD, FRCP

From the Department of Cardiovascular Medicine (J.C., S.L., A.M., G.D.), Royal Postgraduate Medical School, Hammersmith Hospital and the Department of Pharmacology (N.B., D.W.), St. George's Hospital, London, UK.
N.B. is a Wellcome Research Fellow. A.M. is British Heart Foundation Professor of Cardiovascular Medicine.

Address for correspondence: Dr. John Clarke, Department of Cardiovascular Medicine, Hammersmith Hospital, DuCane Road, London W12 OHS, UK.

Received November 16, 1988; revision accepted October 16, 1990.

Circulation 83(3):p 774-777, March 1991.

Background

There is increasing evidence that neuropeptide Y (NPY) contributes to the autonomic control of the circulation. NPY coexists with noradrenaline in perivascular nerve terminals, may be released during sympathetic stimulation, and is a potent constrictor of the human coronary circulation and other vascular beds. In vitro studies show that NPY can act either directly on vascular smooth muscle or indirectly by modulation of the presynaptic release or the postsynaptic actions of noradrenaline. It is unclear to what extent these mechanisms operate in vivo.

Methods and Results

The effect on forearm blood flow of intra-arterial NPY was studied in six volunteers during coinfusion of noradrenaline and during reflex sympathetic stimulation induced by lower-body negative pressure. NPY alone induced a dose-dependent reduction of forearm blood flow in all subjects studied, to a maximum of 49 + 6.1%. The reduction of flow during infusion of noradrenaline alone was 42 ± 8%. The response to noradrenaline was unaffected by coinfusion of a threshold constrictor dose of NPY (50 pmol/min). Furthermore, the reflex sympathetic vasoconstrictor response to 20 cm H20 of lower-body negative pressure was similar in both the infused and control arms during the infusion of 50 pmol/min NPY. The response to noradrenaline was abolished by a-blockade with phentolamine, but the flow reduction induced by NPY was unaffected by a-blockade.

Conclusions

NPY is a potent constrictor of human forearm resistance vessels and has a direct effect independent of a- receptors. NPY has no detectable modulating effect in vivo on the action of endogenous or infused noradrenaline. (Circulation 1991;83:774–777)